Dataset Information

Imaging Cortical Dynamics in GCaMP Transgenic Rats with a Head-Mounted Widefield Macroscope.

ABSTRACT: Widefield imaging of calcium dynamics is an emerging method for mapping regional neural activity but is currently limited to restrained animals. Here we describe cScope, a head-mounted widefield macroscope developed to image large-scale cortical dynamics in rats during natural behavior. cScope provides a 7.8 × 4 mm field of view and dual illumination paths for both fluorescence and hemodynamic correction and can be fabricated at low cost using readily attainable components. We also report the development of Thy-1 transgenic rat strains with widespread neuronal expression of the calcium indicator GCaMP6f. We combined these two technologies to image large-scale calcium dynamics in the dorsal neocortex during a visual evidence accumulation task. Quantitative analysis of task-related dynamics revealed multiple regions having neural signals that encode behavioral choice and sensory evidence. Our results provide a new transgenic resource for calcium imaging in rats and extend the domain of head-mounted microscopes to larger-scale cortical dynamics. VIDEO ABSTRACT.

SUBMITTER: Scott BB

PROVIDER: S-EPMC6283673 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Imaging Cortical Dynamics in GCaMP Transgenic Rats with a Head-Mounted Widefield Macroscope.

Scott Benjamin B BB Thiberge Stephan Y SY Guo Caiying C Tervo D Gowanlock R DGR Brody Carlos D CD Karpova Alla Y AY Tank David W DW

Neuron 20181025 5

Widefield imaging of calcium dynamics is an emerging method for mapping regional neural activity but is currently limited to restrained animals. Here we describe cScope, a head-mounted widefield macroscope developed to image large-scale cortical dynamics in rats during natural behavior. cScope provides a 7.8 × 4 mm field of view and dual illumination paths for both fluorescence and hemodynamic correction and can be fabricated at low cost using readily attainable components. We also report the de ...[more]

PMID: 30482694

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Project description:SignificanceIntrinsic optical signals (IOS) generated in the cortical tissue as a result of various interacting metabolic processes are used extensively to elucidate the underlying mechanisms that govern neurovascular coupling. However, current IOS measurements still often rely on bulky, tabletop imaging systems, and there remains a dearth of studies in freely moving subjects. Lightweight, miniature head-mounted imaging devices provide unique opportunities for investigating cortical dynamics in small animals under a variety of naturalistic behavioral settings.AimThe aim of this work was to monitor IOS in the somatosensory cortex of wild-type mice by developing a lightweight, biocompatible imaging device that readily lends itself to animal experiments in freely moving conditions.ApproachHerein we describe a method for realizing long-term IOS imaging in mice using a 0.54-g, compact, CMOS-based, head-mounted imager. The two-part module, consisting of a tethered sensor plate and a base plate, allows facile assembly prior to imaging sessions and disassembly when the sensor is not in use. LEDs integrated into the device were chosen to illuminate the cortical mantle at two different wavelengths in the visible regime (λcenter: 535 and 625 nm) for monitoring volume- and oxygenation state-dependent changes in the IOS, respectively. To test whether the system can detect robust cortical responses, we recorded sensory-evoked IOS from mechanical stimulation of the hindlimbs (HL) of anesthetized mice in both acute and long-term implantation conditions.ResultsCortical IOS recordings in the primary somatosensory cortex hindlimb receptive field (S1HL) of anesthetized mice under green and red LED illumination revealed robust, multiphasic profiles that were time-locked to the mechanical stimulation of the contralateral plantar hindpaw. Similar intrinsic signal profiles observed in S1HL at 40 days postimplantation demonstrated the viability of the approach for long-term imaging. Immunohistochemical analysis showed that the brain tissue did not exhibit appreciable immune response due to the device implantation and operation. A proof-of-principle imaging session in a freely behaving mouse showed minimal locomotor impediment for the animal and also enabled estimation of blood flow speed.ConclusionsWe demonstrate the utility of a miniature cortical imaging device for monitoring IOS and related hemodynamic processes in both anesthetized and freely moving mice, cueing potential for applications to some neuroscientific studies of sensation and naturalistic behavior.

Project description:Understanding the relationship between brain function and natural behavior remains a significant challenge in neuroscience because there are very few convincing imaging/recording tools available for the evaluation of awake and freely moving animals. Here, we employed a miniaturized head-mounted scanning photoacoustic imaging (hmPAI) system to image real-time cortical dynamics. A compact photoacoustic (PA) probe based on four in-house optical fiber pads and a single custom-made 48-MHz focused ultrasound transducer was designed to enable focused dark-field PA imaging, and miniature linear motors were included to enable two-dimensional (2D) scanning. The total dimensions and weight of the proposed hmPAI system are only approximately 50 × 64 × 48 mm and 58.7 g (excluding cables). Our ex vivo phantom experimental tests revealed that a spatial resolution of approximately 0.225 mm could be achieved at a depth of 9 mm. Our in vivo results further revealed that the diameters of cortical vessels draining into the superior sagittal sinus (SSS) could be clearly imaged and continuously observed in both anesthetized rats and awake, freely moving rats. Statistical analysis showed that the full width at half maximum (FWHM) of the PA A-line signals (relative to the blood vessel diameter) was significantly increased in the selected SSS-drained cortical vessels of awake rats (0.58 ± 0.17 mm) compared with those of anesthetized rats (0.31 ± 0.09 mm) (p < 0.01, paired t-test). In addition, the number of pixels in PA B-scan images (relative to the cerebral blood volume (CBV)) was also significantly increased in the selected SSS-drained blood vessels of awake rats (107.66 ± 23.02 pixels) compared with those of anesthetized rats (81.99 ± 21.52 pixels) (p < 0.01, paired t-test). This outcome may result from a more active brain in awake rats than in anesthetized rats, which caused cerebral blood vessels to transport more blood to meet the increased nutrient demand of the tissue, resulting in an obvious increase in blood vessel volume. This hmPAI system was further validated for utility in the brains of awake and freely moving rats, showing that their natural behavior was unimpaired during vascular imaging, thereby providing novel opportunities for studies of behavior, cognition, and preclinical models of brain diseases.

Dataset Information

Imaging Cortical Dynamics in GCaMP Transgenic Rats with a Head-Mounted Widefield Macroscope.

Publications

Imaging Cortical Dynamics in GCaMP Transgenic Rats with a Head-Mounted Widefield Macroscope.

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